The inability of the myocardial cell to sustain life following ischemic injury still remains the main reason for mortality in the western world. The extent of such events is critical for the determination of the outcome of the patient when non-sudden death occurs. Although the initial consequences of a myocardial ischemic attack is contractile failure, nevertheless, the loss of contractile does not necessarily imply the cells are dead. The applicants proposed to determine noninvasively (for ultimate clinical applications) the part and extent ATP plays in the transition from life to death in the heart following ischemic injury. The primary source of energy is the conversion of the chemical energy of ATP - via oxidative phosphorylation - to mechanical work. This stratagem is the only metabolic process that can provide enough energy to support this continuous contractile process of the heart. Oxygen delivered by the blood supports high energy phosphate (HEP) production via oxidative phosphorylation. When blood flow is insufficient, HEPs begin their markedly spiral downward. Jennings et al., have determined that one of the criteria for myocardial cell death is a reduction in ATP concentration (IATPI) to 10% of control. The measurement of HEPs concentration could help delineate the threshold which myocytes crossover to the inability to sustain life (non-viability). Therefore, the applicants proposed to test the hypothesis that the deter-mination of ATP concentration is a measure of myocardial lethal injury or death. The key to this hypothesis is that viable cells tolerate ATP levels to a certain low level for a certain sustained period of time and after that cell death occurs. To test this hypothesis, the proposal will utilize a 4.l T whole-body MR spectrometer to perform three in-vivo Specific Aims which logically progress from phantom/control; to canine models of various ischemic duration; to clinical applications in a patient population with known cardiovascular disease.
| Straeter-Knowlen, Ingrid M; Butterworth, Edward J; Buchthal, Steven D et al. (2002) PCr overshoot': a study of the duration in canine myocardium. NMR Biomed 15:52-9 |
